Regulation of folate and one-carbon metabolism in mammalian cells. IV. Role of folylpoly-gamma-glutamate synthetase in methotrexate metabolism and cytotoxicity.
作者： J.S. Kim , K.E. Lowe , B Shane
DOI: 10.1016/S0021-9258(20)80595-X
关键词:
摘要: Chinese hamster ovary (CHO) cells expressing human and Escherichia coli folylpoly-gamma-glutamate synthetase (FPGS) activities were used as models to study factors regulating the cytotoxicity metabolism of methotrexate (MTX). CHO FPGS metabolized MTX polyglutamates characteristic cells. Cellular accumulation dependent on level activity unaffected by putative gamma-glutamyl hydrolase inhibitors. The sensitivity continuously exposed was not influenced activity. After short term exposure MTX, higher levels more sensitive drug. transported into mitochondria treatment had no effect preexisting mitochondrial folates while cytosolic converted oxidized forms. Mitochondrial folate significantly impaired treatment, suggesting that transport system is specific for reduced folates.
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